Doxorubicin Liposomal Pegylated Dr. Reddy's 2 mg/ml Concentrate for Dispersion for Infusion

Introduction

Package Leaflet: Information for the User

Pegylated Liposomal Doxorubicin Dr. Reddys 2 mg/ml Concentrate for Dispersion for Infusion

doxorubicin, hydrochloride

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Pegylated Liposomal Doxorubicin Dr. Reddys and what is it used for
2. What you need to know before you use Pegylated Liposomal Doxorubicin Dr. Reddys
3. How to use Pegylated Liposomal Doxorubicin Dr. Reddys
4. Possible side effects
5. Storage of Pegylated Liposomal Doxorubicin Dr. Reddys
6. Contents of the pack and other information

1. What is Pegylated Liposomal Doxorubicin Dr. Reddys and what is it used for

Pegylated liposomal doxorubicin is an antitumor agent.

This medicine is used to treat breast cancer in patients with a risk of heart problems. Pegylated liposomal doxorubicin is also used to treat ovarian cancer. It is used to kill the cancer cells, reduce the size of the tumor, slow down the growth of the tumor, and increase survival.

Pegylated liposomal doxorubicin is also used in combination with another medicine, bortezomib, for the treatment of multiple myeloma (a blood cancer) in patients who have received at least one previous treatment.

This medicine is also used to produce an improvement in Kaposi's sarcoma, including flattening, thinning, and even reduction of the cancer. Other symptoms of Kaposi's sarcoma, such as swelling around the tumor, may also improve or disappear.

Pegylated liposomal doxorubicin contains a medicine that interacts with cells in such a way that it selectively kills cancer cells. The doxorubicin hydrochloride in pegylated liposomal doxorubicin is enclosed in tiny spheres called pegylated liposomes that facilitate the release of the medicine from the bloodstream into the cancerous tissue before it reaches normal, healthy tissue.

2. What you need to know before you use Pegylated Liposomal Doxorubicin Dr. Reddys

Do not use Pegylated Liposomal Doxorubicin Dr. Reddys

• if you are allergic to doxorubicin hydrochloride, peanuts, or soy, or to any of the other ingredients of this medicine (listed in section 6).

Warnings and Precautions

Tell your doctor if you have:

• if you are receiving any treatment for heart or liver disease;
• if you are diabetic, as pegylated liposomal doxorubicin contains sugar and may require adjustment of your diabetes treatment;
• if you have Kaposi's sarcoma and have had your spleen removed;
• if you notice ulcers, discoloration, or any discomfort in your mouth.

There have been reports of interstitial lung disease in patients receiving pegylated liposomal doxorubicin, including fatal cases. The symptoms of interstitial lung disease are cough and difficulty breathing, sometimes with fever, which are not caused by physical activity. Seek medical attention immediately if you experience symptoms indicative of interstitial lung disease.

Children and Adolescents

Pegylated liposomal doxorubicin must not be used in children and adolescents, as it is not known how it will affect them.

Using Pegylated Liposomal Doxorubicin Dr. Reddys with Other Medicines

Tell your doctor or pharmacist

• if you are using or have recently used any other medicines, including those obtained without a prescription;
• about other anticancer treatments you are receiving or have received, as special care is needed with treatments that reduce the number of white blood cells, as they can cause a further reduction in the number of white blood cells. If you are not sure about the treatments you have received or the diseases you have had, discuss this with your doctor.

Pregnancy and Breastfeeding

Consult your doctor or pharmacist before using any medicine.

Since the active ingredient doxorubicin hydrochloride in pegylated liposomal doxorubicin can cause birth defects, it is essential that you contact your doctor if you think you are pregnant.

Women must avoid becoming pregnant and use contraceptive methods while being treated with pegylated liposomal doxorubicin and for eight months after finishing treatment. To avoid pregnancy in their partners, men must use contraceptive methods during and up to six months after treatment with pegylated liposomal doxorubicin.

Since doxorubicin hydrochloride can be harmful to infants, women must stop breastfeeding before starting treatment with pegylated liposomal doxorubicin. Health experts recommend that HIV-infected women should not breastfeed their children under any circumstances to avoid transmitting HIV.

Driving and Using Machines

Do not drive or operate tools or machines if you feel tired or drowsy as a result of treatment with pegylated liposomal doxorubicin.

Pegylated Liposomal Doxorubicin Dr. Reddys Contains Soybean Oil and Sodium

This medicine contains soybean oil. Do not use this medicine if you are allergic to peanuts or soy.

Pegylated liposomal doxorubicin Dr. Reddys contains less than 1 mmol of sodium (23 mg) per dose; i.e., it is essentially "sodium-free".

3. How to Use Pegylated Liposomal Doxorubicin Dr. Reddys

Pegylated liposomal doxorubicin is a formulation with particular characteristics. Therefore, it must not be exchanged with other medicines that also contain doxorubicin hydrochloride.

How Much Pegylated Liposomal Doxorubicin Dr. Reddys is Administered

If you are being treated for breast or ovarian cancer, you will be given pegylated liposomal doxorubicin at a dose of 50 mg per square meter of your body surface area (which is calculated from your height and weight). The dose is repeated every 4 weeks while the disease does not progress and you can tolerate the treatment.

If you are being treated for multiple myeloma and have received at least one previous treatment, you will be given pegylated liposomal doxorubicin at a dose of 30 mg per square meter of your body surface area (based on your height and weight) in a 1-hour intravenous infusion on day 4 of the 3-week bortezomib regimen and immediately after bortezomib infusion. The dose will be repeated as long as you respond satisfactorily and tolerate the treatment.

If you are being treated for Kaposi's sarcoma, you will be given pegylated liposomal doxorubicin at a dose of 20 mg per square meter of your body surface area (which is calculated from your height and weight). The dose is repeated every 2 to 3 weeks for 2 to 3 months and then as frequently as necessary to maintain improvement of your condition.

How Pegylated Liposomal Doxorubicin Dr. Reddys is Administered

Your doctor will administer pegylated liposomal doxorubicin to you through a drip (infusion) in a vein. Depending on the dose and indication, this can take from 30 minutes to over an hour (i.e., 90 minutes).

If You Use More Pegylated Liposomal Doxorubicin Dr. Reddys Than You Should

Acute overdosing worsens side effects such as mouth ulcers or decreases the number of white blood cells and platelets in the blood. Treatment will include the administration of antibiotics, platelet transfusions, use of factors that stimulate the production of white blood cells, and symptomatic treatment of mouth ulcers.

If you are given more doxorubicin than you should, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, stating the medicine and the amount administered.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

During the infusion of pegylated liposomal doxorubicin, the following reactions may occur:

• severe allergic reaction that can include swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing or breathing; itchy rash (hives)
• inflammation and narrowing of the airways, causing cough, wheezing, and difficulty breathing (asthma)
• flushing, sweating, chills, or fever
• chest pain or discomfort
• back pain
• increased or decreased blood pressure
• rapid heartbeat
• seizures (convulsions)

A leak of the injection fluid from the veins into the tissue under the skin can occur. If the infusion stings or hurts when you are receiving a dose of pegylated liposomal doxorubicin, tell your doctor immediately.

Contact your doctor immediately if you notice any of the following serious side effects:

• you have a fever, feel tired, or have signs of bruising or bleeding (very common)
• redness, swelling, peeling, or pain on palpation, mainly on hands or feet (hand-foot syndrome). These effects have been seen very frequently and, sometimes, are severe. In severe cases, these effects can interfere with certain daily activities and can last up to 4 weeks or more before they are completely resolved. Your doctor may delay the start and/or reduce the dose of the next treatment (see below, Strategies to prevent and treat hand-foot syndrome)
• mouth sores, severe diarrhea, or vomiting or nausea (very common)
• infections (frequent), including lung infections (pneumonia) or infections that can affect your vision
• difficulty breathing (frequent)
• severe stomach pain (frequent)
• severe weakness (frequent)
• severe allergic reaction that can include swelling of the face, lips, mouth, tongue, or throat; difficulty swallowing or breathing; itchy rash (hives) (uncommon)
• cardiac arrest (the heart stops beating); heart failure, in which the heart does not pump enough blood to the rest of the body, which can cause difficulty breathing and can cause swelling of the legs (uncommon)
• formation of blood clots that reach the lungs, causing chest pain and difficulty breathing (uncommon)
• swelling, heat, or pain on palpation in any area of the leg, sometimes with pain that worsens when standing or walking (rare)
• severe rash with blisters and peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome) or on most of the body (toxic epidermal necrolysis) (rare)

Other Side Effects

The following may occur between infusions:

Very Common Side Effects(may affect more than 1 in 10 patients)

• decrease in the number of white blood cells, which can increase the risk of infection. In rare cases, the decrease in white blood cells can lead to a severe infection. Anemia (decrease in red blood cells) can cause fatigue, and a decrease in platelets in the blood can increase the risk of bleeding. Due to possible changes in your blood cells, you will be subject to regular blood tests
• loss of appetite
• constipation
• skin rash, including redness of the skin, allergic skin rash, bumpy or red rash on the skin
• hair loss
• pain, including muscle pain and chest pain, joint pain, arm or leg pain
• feeling very tired

Common Side Effects(may affect up to 1 in 10 patients)

• infections, including severe infection throughout the body (sepsis), lung infections, herpes zoster virus infections (herpes), a type of bacterial infection (mycobacterium avium complex infection), urinary tract infections, fungal infections (including thrush and oral thrush in the mouth), infection of the hair follicles, infection or irritation of the throat, infection of the nose, nasal passages, or throat (cold)
• low number of a type of white blood cell (neutrophils), with fever
• severe weight loss and muscle weakness, insufficient water in the body (dehydration), low levels of potassium, sodium, or calcium in the blood
• feeling confused, anxious, depressed, difficulty sleeping
• nerve damage that can cause tingling, numbness, pain, or loss of pain sensation, nerve pain, strange sensation in the skin (such as tingling or prickling), decreased sensitivity, especially in the skin
• change in taste, headache, feeling very sleepy with little energy, feeling dizzy
• eye inflammation (conjunctivitis)
• rapid heartbeat
• increased or decreased blood pressure, facial flushing
• difficulty breathing that may appear after physical activity, nosebleeds, cough
• inflammation of the stomach lining or esophagus, mouth ulcers, indigestion, difficulty swallowing, mouth pain, dry mouth
• skin problems, including dry or scaly skin, allergic rash, ulcers or blisters on the skin, skin discoloration, change in skin pigmentation, small red or purple spots caused by bleeding under the skin, nail problems, acne
• excessive sweating
• muscle spasms or cramps
• pain that affects muscles, bones, or back
• pain when urinating
• allergic reaction to the infusion of the medicine, flu-like illness, chills, inflammation of the mucous membranes of different body cavities and ducts, such as the nose, mouth, or trachea, feeling weak, general feeling of discomfort, swelling caused by fluid retention, feeling of swelling of hands, ankles, or feet
• weight loss

When pegylated liposomal doxorubicin is used as a single medicine, it is less likely that some of these side effects will occur, and some of them have never been reported.

Uncommon Side Effects(may affect up to 1 in 100 patients)

• herpes simplex virus infections (cold sores or genital herpes), fungal infections
• low number of all types of blood cells, increased number of 'platelets' (cells that help blood clot)
• allergic reaction
• high potassium levels in the blood, low magnesium levels in the blood
• nerve damage that affects more than one area of the body
• seizures (convulsions), fainting
• unpleasant or painful sensation, especially to touch, drowsiness
• blurred vision, watery eyes
• sensation of rapid or irregular heartbeat (palpitations), heart muscle disease, heart damage
• tissue damage (necrosis) at the injection site, inflammation of the veins that causes swelling and pain, feeling dizzy when sitting or standing up
• chest discomfort
• gas, inflamed gums (gingivitis)
• skin problems or rashes, including dry or scaly skin, allergic rash, ulcers or blisters on the skin, skin discoloration, change in skin pigmentation, small red or purple spots caused by bleeding under the skin, nail problems, acne
• muscle weakness
• breast pain
• irritation or pain at the injection site
• swollen face, elevated body temperature
• symptoms (such as inflammation, redness, or pain) in areas of the body that have been previously treated with radiation therapy or that have been damaged as a result of an intravenous injection of chemotherapy

Rare Side Effects(may affect up to 1 in 1,000 patients)

• infection that occurs in people with a weakened immune system
• low number of blood cells produced in the bone marrow
• inflammation of the retina, which can cause changes in vision or blindness
• abnormal heartbeat, abnormal tracing on an electrocardiogram (ECG) that can occur with low heart rate, heart problem that affects heart rate and rhythm, bluish discoloration of the skin and mucous membranes caused by low oxygen levels in the blood
• dilation of blood vessels
• feeling of pressure in the throat
• sores and swelling on the tongue, ulcers on the lips
• skin rash with blisters filled with fluid
• vaginal infection, redness of the scrotum
• problems with the mucous membranes of different body cavities and ducts, such as the nose, mouth, or trachea
• abnormal results in liver blood tests, increased "creatinine" levels in the blood

Side Effects of Unknown Frequency(cannot be estimated from the available data)

• blood cancer that develops rapidly and affects blood cells (acute myeloid leukemia), bone marrow disease that affects blood cells (myelodysplastic syndrome), mouth or lip cancer
• cough and difficulty breathing, possibly accompanied by fever, which are not caused by physical activity (interstitial lung disease)

Adverse Reaction Reporting

If you experience any type of adverse reaction, consult your doctor or nurse, even if it is a possible adverse reaction that does not appear in this prospectus. You can also report it directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse reactions, you can contribute to providing more information on the safety of this medication.

Strategies to prevent and treat hand-foot syndrome include:

• soaking hands and/or feet in containers with cold water when possible (e.g., while watching TV, reading, or listening to the radio);
• keeping hands and feet uncovered (without gloves, socks, etc.);
• staying in cool places;
• taking cold water baths when it's hot;
• avoiding strenuous exercise that may cause trauma to the feet (e.g., jogging);
• avoiding exposure of the skin to very hot water (e.g., jacuzzis, saunas);
• avoiding tight-fitting shoes or high-heeled shoes.

Pyridoxine (Vitamin B6):

• Vitamin B6 is available without a prescription;
• take 50-150 mg per day starting when the first signs of redness or tingling appear.

5. Storage of Pegylated Liposomal Doxorubicin

Keep this medication out of sight and reach of children.

Store in the refrigerator (between 2°C and 8°C). Do not freeze. Keep in the original packaging to protect from light.

After dilution:

The chemical and physical stability has been verified during use, for a period of 24 hours between 2°C and 8°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, the storage periods during use and the conditions before use are the responsibility of the user and should not exceed 24 hours between 2°C and 8°C. Partially used vials should be discarded.

Do not use this medication after the expiration date shown on the label and carton.

Do not use this medication if you observe evidence of precipitation or presence of particles.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Pegylated Liposomal Doxorubicin Dr. Reddy's

• The active ingredient is doxorubicin hydrochloride. One ml of Pegylated Liposomal Doxorubicin contains 2 mg of doxorubicin hydrochloride in a pegylated liposomal formulation.
• The other components are ?-(2-[1,2-distearoyl-sn-glycero(3)phosphoxy]ethylcarbamoyl)-?-methoxypoly(oxethylene)-40 sodium salt (MPEG-DSPE), fully hydrogenated soy phosphatidylcholine (HSPC), cholesterol, ammonium sulfate, sucrose, histidine, water for injectable preparations, hydrochloric acid (for pH adjustment), and sodium hydroxide (for pH adjustment). See section 2.

Pegylated Liposomal Doxorubicin Dr. Reddy's concentrate for dispersion for infusion: vials providing 10 ml (20 mg) or 25 ml (50 mg).

Appearance and Package Contents of the Product

Pegylated Liposomal Doxorubicin Dr. Reddy's is sterile, translucent, and red. Pegylated Liposomal Doxorubicin Dr. Reddy's is available in individual containers or in packs of ten vials, made of glass.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Reddy Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona

Spain

Manufacturer

betapharm Arzneimittel GmbH

Kobelweg 95

86156 Augsburg

Germany

or

Rual Laboratories SRL

313, Splaiul Unirii, Building H,

1st floor, sector 3, Bucharest, 030138

Romania

or

DR. REDDY'S LABORATORIES ROMÂNIA S.R.L.

Space 2 Sector 1 30-32 Strada Daniel

Danielopolu 5th Floor

Bucharest, 014134

Romania

or

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park,

Paola PLA 3000

Malta

This medication is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) with the following names:

Date of the last revision of this prospectus:September 2024

Detailed information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

This information is intended only for doctors or healthcare professionals (see section 3):

Caution should be exercised when handling a dispersion of Pegylated Liposomal Doxorubicin. The use of gloves is required. In case Pegylated Liposomal Doxorubicin comes into contact with skin or mucous membranes, wash the affected area immediately with water and soap. Pegylated Liposomal Doxorubicin should be handled and disposed of as other anticancer medications.

Determine the dose of Pegylated Liposomal Doxorubicin to be administered (based on the recommended dose and the patient's body surface area). Take the appropriate volume of Pegylated Liposomal Doxorubicin in a sterile syringe. Strict aseptic measures should be followed since Pegylated Liposomal Doxorubicin does not contain any preservative or bacteriostatic agent. The appropriate dose of Pegylated Liposomal Doxorubicin should be diluted in a 5% glucose solution (50 mg/ml) before administration. For doses <90 mg, dilute pegylated liposomal doxorubicin in 250 ml, and for doses ≥ 90 500 ml.< p>

To minimize the risk of infusion reactions, the initial dose is administered at a rate not exceeding 1 mg/minute. If no infusion reaction is observed, subsequent infusions of Pegylated Liposomal Doxorubicin can be administered over a period of 60 minutes.

In the clinical trial program in breast cancer, modification of the infusion was allowed in patients who experienced an infusion reaction as follows: 5% of the total dose was infused slowly over the first 15 minutes. If tolerated without reaction, the infusion rate was doubled over the next 15 minutes. If tolerated, the infusion was completed over the next hour for a total infusion time of 90 minutes.

If the patient experiences early symptoms or signs of an infusion reaction, interrupt the infusion immediately, administer appropriate symptomatic treatment (antihistamine and/or short-acting corticosteroid), and resume at a slower rate.

The use of any diluent other than 5% glucose solution (50 mg/ml), or the presence of any bacteriostatic agent, such as benzyl alcohol, may cause precipitation of Pegylated Liposomal Doxorubicin.